Assessing ethanol's actions in the suprachiasmatic circadian clock using in vivo and in vitro approaches

Abstract

Research over the past decade has demonstrated substantial interactions between the circadian system and the processes through which alcohol affects behavior and physiology. Here we summarize the results of our collaborative efforts focused on this intersection. Using a combination of in vivo and in vitro approaches, we have shown that ethanol affects many aspects of the mammalian circadian system, both acutely as well as after chronic administration. Conversely, we have shown circadian influences on ethanol consumption. Importantly, we are beginning to delve into the cellular mechanisms associated with these effects. We are also starting to form a picture of the neuroanatomical bases for many of these actions. Finally, we put our current findings into perspective by suggesting new avenues of inquiry for our future efforts.

Chronic Alcohol Consumption in Rats Leads to Desynchrony in Diurnal Rhythms and Molecular Clocks

“…Much effort has gone into determining whether alcohol affects the SCN using various in vivo and in vitro approaches (Prosser and Glass, 2014). Previous studies suggested that chronic alcohol had little effect on the ability of the SCN to entrain to external L:D cycles (Brager et al, 2010), consistent with our results that rats exhibited robust 24-hour periodicities in temperature and activity under a 12:12 L:D cycle.…”

Dissociation between diurnal cycles in locomotor activity, feeding behavior and hepatic PERIOD2 expression in chronic alcohol-fed mice

“…Chronic alcohol consumption could possibly impact the master clock in the SCN (Prosser & Glass, 2014), thereby altering feeding and locomotor activity rhythms. For example, in rats a year-long alcohol exposure resulted in the depression of key SCN neuropeptides (Madeira et al, 1997), and a 2-week alcohol liquid diet altered the SCN rhythmic expression profiles of the clock genes per2 and per3 (Chen, Kuhn, Advis, & Sarkar, 2004).…”

“…As discussed above, chronic alcohol-induced body temperature change and fragmented sleeping patterns appear to shift behaviors, which likely contribute to the phase shift in the hepatic clock. Interestingly, the clock genes per1 , per2, and NPAS2 , that exhibit altered expression patterns in the steatotic liver under CAF (Zhou et al, 2014), have also been shown to contribute to the regulation of behaviors associated with feeding or alcohol preference: per2 mutant mice exhibit enhanced alcohol preference/intake (Spanagel et al, 2005), including increased free-choice ethanol drinking bouts during both the dark and light phases of the LD cycle (Prosser & Glass, 2014); per1 mutant mice display an altered feeding rhythm (Liu et al, 2014); and NPAS2 null mice exhibit delayed anticipatory locomotor activity in response to restricted feeding (Dudley et al, 2003). Lastly, a dampened plasma cortisol rhythmicity has been reported in chronic-alcohol liver disease patients (Rosman et al, 1982).…”

The dynamics of GABA signaling: Revelations from the circadian pacemaker in the suprachiasmatic nucleus

“…Ethanol can modulate the phase shifting effects of photic and non-photic stimuli (for a review see Prosser and Glass, 2015), although chronic consumption of ethanol in a light-dark cycle does not alter the phase of the circadian pacemaker in the SCN (Filiano et al, 2013). In hamsters, systemic administration of ethanol attenuates light-induced phase advances without affecting phase delays (Seggio et al, 2007; Ruby et al, 2009a, 2009b).…”